{"id":"23db5314-34c1-5192-b7f5-18a542fc0a3e","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-gsr-nadph-to-fad","predicate":"reduces","statement":"Human GSR substrate structures place NADPH for hydride transfer to bound FAD, the first redox step in glutathione recycling.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"56016ef3-6343-55fd-879b-7b005641aeb0","mechanism_event_label":"NADPH supplies electrons to the B2-derived cofactor.","subject":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"object":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"56016ef3-6343-55fd-879b-7b005641aeb0","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-gsr-nadph-to-fad-event","event_type":"biochemical_relationship","label":"NADPH supplies electrons to the B2-derived cofactor.","description":"Human GSR substrate structures place NADPH for hydride transfer to bound FAD, the first redox step in glutathione recycling.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ae04c12f-c0ac-5c8d-9ee2-76e58156d105","slug":"gsr","display_name":"Glutathione reductase / GSR","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"electron donor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"role":"electron acceptor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Nicotinamide-containing NADPH and B2-derived FAD perform distinct functions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Purified-enzyme assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Structural support for the established catalytic cycle; radiation reduction must be distinguished from natural catalysis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Riboflavin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"NADPH supplies electrons to the B2-derived cofactor.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified human erythrocyte-type GSR crystals","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"98730067-6473-5d56-8e96-220d76a78be3","evidence_kind":"source_excerpt","locator":"Lines 1304-1316","start_line":1304,"end_line":1316,"excerpt":"### b2-gsr-nadph-to-fad\nHuman GSR substrate structures place NADPH for hydride transfer to bound FAD, the first redox step in glutathione recycling.\nCondition category: normal\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: NADPH supplies electrons to the B2-derived cofactor.\norganism: Homo sapiens\ntissue_or_cell_type: Purified human erythrocyte-type GSR crystals\nexperimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.\nlimitations: Structural support for the established catalytic cycle; radiation reduction must be distinguished from natural catalysis.\nexposure: Purified-enzyme assay\ncross_nutrient: Nicotinamide-containing NADPH and B2-derived FAD perform distinct functions.\nevidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes\n[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. 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